Web Release Date: April 11,
The Influence of Macromolecular Crowding on HIV-1 Protease Internal Dynamics
and
Department of Chemistry & Biochemistry, Center for Theoretical Biological Physics, Department of Pharmacology, Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California 92093-0365, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University, 02-106 Warsaw, Poland, and NEST Scuola Normale Superiore, Piazza dei Cavalieri, 7 I-56126 Pisa, Italy
Received January 20, 2006
Abstract:
High macromolecular concentrations, or crowded conditions, have been shown to affect a wide variety of molecular processes, including diffusion, association and dissociation, and protein folding and stability. Here, we model the effect of macromolecular crowding on the internal dynamics of a protein, HIV-1 protease, using Brownian dynamics simulations. HIV-1 protease possesses a pair of flaps which are postulated to open in the early stages of its catalytic mechanism. Compared to low concentrations, close-packed concentrations of repulsive crowding agents are found to significantly reduce the fraction of time that the protease flaps are open. Macromolecular crowding is likely to have a major effect on in vivo enzyme activity, and may play an important regulatory role in the viral life cycle.
Download the full text: PDF | HTML
